A Virulent PEDV Strain FJzz1 with Genomic Mutations and Deletions at the High Passage Level Was Attenuated in Piglets via Serial Passage In Vitro

Highly virulent porcine epidemic diarrhea virus (PEDV) strains re-emerged and circulated in China at the end of 2010, causing significant economic losses in the pork industry worldwide. To understand the genetic dynamics of PEDV during its passage in vitro, the PEDV G2 strain FJzz1 was serially propagated in Vero cells for up to 200 passages. The susceptibility and adaptability of the FJzz1 strain increased gradually as it was serially passaged in vitro. Sequence analysis revealed that amino acid (aa) changes were mainly concentrated in the S glycoprotein, which accounted for 72.22%–85.71% of all aa changes. A continuous aa deletion ((55)I(56)G(57)E → (55)K(56)Δ(57)Δ) occurred in the N-terminal domain of S1 (S1-NTD). To examine how the aa changes affected its virulence, FJzz1-F20 and FJzz1-F200 were selected to simultaneously evaluate their pathogenicity in suckling piglets. All the piglets in the FJzz1-F20-infected group showed typical diarrhea at 24 h postinfection, and the piglets died successively by 48 h postinfection. However, the clinical signs of the piglets in the FJzz1-F200-infected group were significantly weaker, and no deaths occurred. The FJzz1-F200-infected group also showed a lower level of fecal viral shedding and lower viral loads in the intestinal tissues, and no obvious histopathological lesions. Type I and III interferon were induced in the FJzz1-F200 infection group, together with pro-inflammatory cytokines, such as TNF-α, IL-1β and IL-8. These results indicate that the identified genetic changes may contribute to the attenuation of FJzz1 strain, and the attenuated FJzz1-F200 may have the potential for developing PEDV live-attenuated vaccines. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12250-021-00368-w.